Variant rs3793801 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020549.5(CHAT):c.2067C>T(p.Ile689=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,614,196 control chromosomes in the GnomAD database, including 2,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 266 hom., cov: 32)

Exomes 𝑓: 0.015 ( 2344 hom. )

Consequence

CHAT
NM_020549.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

CHAT (HGNC:1912): (choline O-acetyltransferase) This gene encodes an enzyme which catalyzes the biosynthesis of the neurotransmitter acetylcholine. This gene product is a characteristic feature of cholinergic neurons, and changes in these neurons may explain some of the symptoms of Alzheimer's disease. Polymorphisms in this gene have been associated with Alzheimer's disease and mild cognitive impairment. Mutations in this gene are associated with congenital myasthenic syndrome associated with episodic apnea. Multiple transcript variants encoding different isoforms have been found for this gene, and some of these variants have been shown to encode more than one isoform. [provided by RefSeq, May 2010]

CHAT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-49664866-C-T is Benign according to our data. Variant chr10-49664866-C-T is described in ClinVar as [Benign]. Clinvar id is 128722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-49664866-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHAT	NM_020549.5 linkuse as main transcript	c.2067C>T	p.Ile689=	synonymous_variant	15/15	ENST00000337653.7	NP_065574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHAT	ENST00000337653.7 linkuse as main transcript	c.2067C>T	p.Ile689=	synonymous_variant	15/15	1	NM_020549.5	ENSP00000337103	P2	P28329-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2344

AN:

152188

Hom.:

268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.0587

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0325

AC:

8179

AN:

251496

Hom.:

893

AF XY:

0.0328

AC XY:

4462

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.0557

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0145

AC:

21210

AN:

1461890

Hom.:

2344

Cov.:

AF XY:

0.0155

AC XY:

11298

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00892

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.0529

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0154

AC:

2339

AN:

152306

Hom.:

266

Cov.:

AF XY:

0.0182

AC XY:

1357

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.0582

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00703

Hom.:

194

Bravo

AF:

0.0150

Asia WGS

AF:

0.149

AC:

516

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 09, 2015	- -

Familial infantile myasthenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: 18

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over